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Dominique Bonneau

Publications and source records attributed to Dominique Bonneau.

7 recordsLinked to original sources
PubMed2025

Pathogenic XPO1 variants cause a dominant neurodevelopmental disorder.

PURPOSE: XPO1 functions in key cellular processes, including nucleo-cytoplasmic export and mitosis. The gene is deleted in a subset of patients with the 2p15p16.1 microdeletion syndrome; however, no monogenic XPO1-related disorder has been described to date. METHODS: We collected clinical data of individuals with de novo XPO1 variants through online matchmaking. We used Drosophila to study XPO1 function in development and habituation learning. RESULTS: A total of 22 individuals met the criteria to be included in the main study cohort. Of these, half have putative loss-of-function variants, and half have coding variants (10 missense and 1 in-frame deletion variant). We found an overlapping phenotype, consistent with a monogenic neurodevelopmental disorder. We demonstrate XPO1 functions in development by ubiquitous and neuron-specific knockdown in Drosophila. GABAergic neuron specific knockdown flies demonstrated impaired habituation. CONCLUSION: Our results establish XPO1 as a novel dominant monogenic neurodevelopmental disorder gene and demonstrate a central role for XPO1 in development.

Exportin 1 Protein↗
PubMed2003

Retinal angioma in a patient with Cowden disease.

PURPOSE: To report a rare case of ocular localization of Cowden disease. DESIGN: Case report. METHODS: A 50-year-old woman with a history of multiple tumors was diagnosed with Cowden disease. A PTEN gene mutation was found. Visual acuity of the left eye had decreased 2 years before diagnosis. RESULTS: Visual acuity was 20/20 in the right eye and 20/200 in the left eye. Right eye fundus examination showed an epiretinal membrane associated with a peripheral and temporal inferior angiomatous lesion. Treatment consisted of cryoapplication and surgical removal of the epiretinal membrane after central vitrectomy. Although the anatomic result was satisfactory, the patient's visual acuity remained unchanged. CONCLUSIONS: Hamartomatous ocular lesions have been described in Cowden disease. We are unaware, however, of such retinal angiomatous lesions in patients with PTEN gene mutations.

Cryosurgery↗
PubMed2002

X-linked lissencephaly with absent corpus callosum and ambiguous genitalia (XLAG): clinical, magnetic resonance imaging, and neuropathological findings.

X-linked lissencephaly with absent corpus callosum and ambiguous genitalia is a newly recognized syndrome responsible for a severe neurological disorder of neonatal onset in boys. Based on the observations of 3 new cases, we confirm the phenotype in affected boys, describe additional MRI findings, report the neuropathological data, and show that carrier females may exhibit neurological and magnetic resonance imaging abnormalities. In affected boys, consistent clinical features of X-linked lissencephaly with absent corpus callosum and ambiguous genitalia are intractable epilepsy of neonatal onset, severe hypotonia, poor responsiveness, genital abnormalities, and early death. On magnetic resonance imaging, a gyration defect consisting of anterior pachygyria and posterior agyria with a moderately thickened brain cortex, dysplastic basal ganglia and complete agenesis of the corpus callosum are consistently found. Neuropathological examination of the brain shows a trilayered cortex containing exclusively pyramidal neurons, a neuronal migration defect, a disorganization of the basal ganglia, and gliotic and spongy white matter. Finally, females related to affected boys may have mental retardation and epilepsy, and they often display agenesis of the corpus callosum. These findings expand the phenotype of X-linked lissencephaly with absent corpus callosum and ambiguous genitalia, may help in the detection of carrier females in affected families, and give arguments for a semidominant X-linked mode of inheritance.

Adult↗
PubMed2002

Decrease in serum leptin after prolonged physical activity in men.

PURPOSE: This study was designed to determine whether serum leptin levels were affected by a 5-d military course after 3 wk of combat training. METHODS: 26 male soldiers (mean age = 21 +/- 2 yr) were examined at the beginning of the training program and just at the end of the 5-d course. The combination of continuous heavy physical activity and sleep deprivation led to energy deficiency. Blood samples were analyzed for serum leptin, insulin, cortisol, adrenocorticotropin (ACTH), and testosterone; plasma was analyzed for free fatty acids (FFA), glycerol, glucose, and catecholamines. RESULTS: At the end of the 5-d course, there was a significant reduction in serum leptin (0.40 +/- 0.04 ng x mL(-1) versus 1.47 +/- 0.14 ng x mL(-1), < 0.001), i.e., a mean decrease of 67.00 +/- 3.75%. Plasma norepinephrine and dopamine rose significantly from 296 +/- 17 ng x L(-1) to 672 +/- 48 ng x L(-1) and 23 +/- 3 ng x L(-1) to 40 +/- 5 ng x L(-1) ( < 0.001 and < 0.01, respectively), whereas epinephrine remained unchanged. Serum concentrations of the anabolic hormone, insulin, fell from 31.17 +/- 3.03 microU x mL(-1) to 17.79 +/- 1.58 microU x mL(-1) ( < 0.001), whereas plasma FFA and glycerol were increased ( < 0.001, < 0.05, respectively). A statistically significant correlation appeared between the changes in leptin and insulin (r = 0.5306, < 0.01). Serum testosterone decreased significantly ( < 0.001), whereas serum cortisol, ACTH, and plasma glucose were unchanged at the end of the course. The training program had no significant effect on mean body mass index. CONCLUSION: A 4-wk strenuous military training program, which induced an energy deficiency, reduced serum leptin to a third of normal levels. The decrease in serum leptin was attributed to the exercise-induced elevation in catecholamines and hypoinsulinemia.

Adult↗